The allylic diazene rearrangement (ADR) is a concerted, pericyclic reaction that has been used to install sp3 stereocenters in cyclic systems. This application details preliminary studies and proposed applications of the ADR in establishing acyclic stereocenters. The methods will likely have broad applications in organic synthesis, in particular total synthesis of marine natural products of biomedical importance. The first aim of the project involves the diastereoselective reduction of acyclic 1'-chiral- 1,2-unsaturated tosyl hydrazones which proceed with in situ ADR to afford products containing either 1,4-syn or 1,4-anti stereorelationships between alkoxy and alkyl substituents. The second aim of the project involves coupling the addition of weak nucleophiles to the ADR. Diastereo- and/or enantioselective additions of crotyl nucleophiles, coupled with the ADR, should afford skipped dienes with 1,4-stereocontrol between alkyl substituents. Diastereo- and/or enantioselective additions of enol silanes and related nucleophiles, coupled with the ADR, offers the potential for carbonyl compound 1-alkenylations. Current methods of 1-alkenylation suffer from lack of substrate scope and/or the need for toxic reagents. PUBLIC HEALTH RELEVANCE: The goal of this project involves development of new asymmetric methods of synthesis that have the potential for improving the ability of the synthetic chemist to prepare stereochemically and functionally complex molecules. In particular, the methods will aid in the total synthesis of biomedically important marine natural products. [unreadable] [unreadable] [unreadable]